An appraisal of respiratory system compliance in mechanically ventilated covid-19 patients

Abstract

Background: Heterogeneous respiratory system static compliance (C_RS) values and levels of hypoxemia in patients with novel coronavirus disease (COVID-19) requiring mechanical ventilation have been reported in previous small-case series or studies conducted at a national level.

Methods: We designed a retrospective observational cohort study with rapid data gathering from the international COVID-19 Critical Care Consortium study to comprehensively describe C_RS-calculated as: tidal volume/[airway plateau pressure-positive end-expiratory pressure (PEEP)]-and its association with ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide.

Results: We studied 745 patients from 22 countries, who required admission to the ICU and MV from January 14 to December 31, 2020, and presented at least one value of C_RS within the first seven days of MV. Median (IQR) age was 62 (52-71), patients were predominantly males (68%) and from Europe/North and South America (88%). C_RS, within 48 h from endotracheal intubation, was available in 649 patients and was neither associated with the duration from onset of symptoms to commencement of MV (p = 0.417) nor with PaO₂/FiO₂ (p = 0.100). Females presented lower C_RS than males (95% CI of C_RS difference between females-males: - 11.8 to - 7.4 mL/cmH₂O p < 0.001), and although females presented higher body mass index (BMI), association of BMI with C_RS was marginal (p = 0.139). Ventilatory management varied across C_RS range, resulting in a significant association between C_RS and driving pressure (estimated decrease - 0.31 cmH₂O/L per mL/cmH₂0 of C_RS, 95% CI - 0.48 to - 0.14, p < 0.001). Overall, 28-day ICU mortality, accounting for the competing risk of being discharged within the period, was 35.6% (SE 1.7). Cox proportional hazard analysis demonstrated that C_RS (+ 10 mL/cm H₂O) was only associated with being discharge from the ICU within 28 days (HR 1.14, 95% CI 1.02-1.28, p = 0.018).

Conclusions: This multicentre report provides a comprehensive account of C_RS in COVID-19 patients on MV. C_RS measured within 48 h from commencement of MV has marginal predictive value for 28-day mortality, but was associated with being discharged from ICU within the same period. Trial documentation: Available at https://www.covid-critical.com/study .

Trial registration: ACTRN12620000421932.

Keywords: ARDS; COVID-19; Compliance; Mechanical ventilation; SARS-CoV-2.

Fig. 1

Patient enrolment rate from January 14 through December 31, 2020

Fig. 2

Patient population flow chart. The analysis of 1505 COVID-19 patients on mechanical ventilation identified 649 patients with static respiratory system compliance within 48 h from commencement of mechanical ventilation

Fig. 3

Linear regression analysis of days from onset of symptoms to commencement of mechanical ventilation and static respiratory system compliance, based on the first measurement obtained within 48 h from commencement of mechanical ventilation, adjusted for body mass index. Dark black horizontal bar depicts median value, and upper and lower horizontal light black bars show 90th and 10th percentile. Days of onset of symptoms to commencement of mechanical ventilation was not associated with static respiratory system compliance (estimate 0.92 mL/cmH₂O, 95% CI − 0.31–0.31 p = 0.417)

Fig. 4

a Linear regression analysis of arterial partial pressure of oxygen (PaO₂/FiO₂) and respiratory system compliance (C_RS), based on the first measurement obtained within 48 h from commencement of mechanical ventilation, with an interaction of gender and adjusted for body mass index (BMI). No statistically significant association was found between PaO₂/FiO₂ and C_RS (estimate 0.49, 95% CI − 0.09–1.07 p = 0.100). Typical acute respiratory distress syndrome stratification groups [35] (severe, moderate and mild based on levels of hypoxemia) are highlighted in dark, medium and light grey, respectively. b Static respiratory system compliance (C_RS) distribution by sex, based on the first measurement obtained within 48 h from commencement of mechanical ventilation. Dashed black lines depict median values for females and males

Fig. 5

Linear regression analysis of static respiratory system compliance, based on the first measurement obtained within 48 h from commencement of mechanical ventilation, and body mass index with an interaction for sex. Per each graph, fitted line of the model is depicted and the upper and lower lines display the 95% predictive interval. Dark grey dots depict female patients, while light grey dots males. Static respiratory system compliance did not vary according to the body mass index (estimate − 0.12 cmH₂O/mL, 95%CI − 0.29 to − 0.04, p = 0.139), but was associated with female sex (estimate − 10.73 cmH₂O/mL, 95%CI − 18.54 to − 2.92, p = 0.007)

Fig. 6

Static respiratory system compliance dynamics. Evolution of static respiratory system compliance over the first 7 days of mechanical ventilation, adjusted for body mass index. Under each day, the number of analysed patients is reported in parenthesis. Fitted line of the model is depicted, and the upper and lower lines display the 95% predictive interval. Respiratory system compliance varied during the first seven days of mechanical ventilation (estimate − 0.31 cmH₂O/mL, 95%CI − 0.48 to 0.14, p < 0.001)

Fig. 7

Linear Mixed model analysis of respiratory system compliance vs. crucial pulmonary variables during the first 7 days of mechanical ventilation (grey-scale coded bar for day 1 through 7 is reported on the right section of each graph and in parenthesis is reported the number of analysed patients). Per each graph, fitted line of the model is depicted and the upper and lower lines display the 95% predictive interval. All analyses are adjusted for body mass index. Static compliance of respiratory system was found to be associated with PaCO₂ (estimated decrease − 0.11 mmHg, 95% CI − 0.15 to − 0.06, p < 0.001), tidal volume (estimated increase 0.04 mL/Kg of predicted body weight per day, 95% CI 0.03–0.04, p < 0.001), PEEP (estimated increase − 0.03 cmH₂O, 95% CI 0.02–0.04, p < 0.001), driving pressure (estimated decrease − 0.31 cmH₂O/L, 95% CI − 0.48 to 0.14, p < 0.001) and FiO₂ (estimated decrease − 0.15%, 95% CI − 0.23 to − 0.06, p < 0.001). While PaO₂/FiO₂, was not significantly associated with static compliance of respiratory system (estimated increase 0.29 mmHg, 95% CI − 0.03 to 0.61, p = 072) PaO₂/FiO_2, ratio between arterial partial pressure of oxygen and inspiratory fraction of oxygen; PaCO₂ arterial partial pressure of carbon dioxide; PEEP, positive end-expiratory pressure

Fig. 8

Association of airway inspiratory plateau pressure with static respiratory system compliance. Linear Mixed model analysis of the association of respiratory system compliance with airway inspiratory plateau pressure during the first 7 days of mechanical ventilation (grey-scale coded bar for day 1 through 7 is reported on the right section of each graph and in parenthesis is reported the number of analysed patients). Fitted line of the model is depicted, and the upper and lower lines display the 95% predictive interval. Analysis is adjusted for body mass index. The model highlights significant association between respiratory system compliance and airway plateau pressure (estimated decrease − 0.22 cmH₂O/L, 95% CI − 0.23 to − 0.21, p < 0.001), but based on the model prediction, airway plateau pressure remained predominantly below 30 cmH₂O

Fig. 9

Multistate modelling and Cox regression analysis outcomes for patient with static compliance recorded within 48 h of commencing mechanical ventilation. a Multistate model structure for estimating expected outcomes up to 28 days from admission to intensive care unit (ICU). Modelled health states include not on invasive mechanical ventilation (non-MV), on mechanical ventilation (MV), ICU discharge and death. Patients start in the non-MV state if not mechanically ventilated upon or prior to ICU admission, or in the MV state otherwise. b Predicted probabilities of occupying health states up to 28 days from ICU admission. c Results of Cox proportional hazards modelling for risk of death and ICU discharge from commencement of mechanical ventilation. Covariates comprise age, body mass index (BMI), selected comorbidities (hypertension, chronic cardiac disease, chronic kidney disease) and baseline static compliance. Parameter estimates are presented as estimated hazard ratios with 95% confidence intervals (CI). Further details on factors significantly associated with assessed outcomes are available in the results section